Direct coupling of fiber-in-tube solid-phase microextraction with tandem mass spectrometry to determine amyloid beta peptides as biomarkers for Alzheimer's disease in cerebrospinal fluid samples

Autor(es)

Souza, Israel D. ; Anderson, Jared L. ; Tumas, Vitor ; Queiroz, Maria Eugenia C.

• Tipo de documento: Artigo Científico
• Fonte: Talanta; v. 254, p. 8-pg., 2023-03-01.

Resumo

Current research efforts at neurological diseases have focused on identifying novel biomarkers to aid in diag-nosis, to provide accurate prognostic information, and to monitor disease progression. This study presents the direct coupling of fiber-in-tube solid-phase microextraction to tandem mass spectrometry as a reliable method to determine amyloid beta peptides (A beta 38, A beta 40, and A beta 42) as biomarkers for Alzheimer's disease in cerebrospinal fluid (CSF) samples. To obtain the biocompatible fiber-in-tube SPME capillary, a PEEK tube segment was longi-tudinally packed with fine fibers [nitinol wires coated with a zwitterionic polymeric ionic liquid], to act as se-lective extraction medium. The fiber-in-tube SPME-MS/MS method integrated analyte extraction/enrichment and sample cleanup (exclusion of interferents) into one step. The method provided lower limits of quantification (LLOQ: 0.2 ng mL-1 for A beta 38 and 0.1 ng mL-1 for A beta 40 and A beta 42), high precision (CV lower than 11.6%), and high accuracy (relative standard deviation lower than 15.1%). This method was successfully applied to deter-mine A beta peptides in CSF samples obtained from AD patients (n = 8) and controls (healthy volunteers, n = 10). Results showed that A beta 42 levels in the CSF samples obtained from AD patients were significantly lower compared to healthy controls (p < 0.05). On the basis of the ROC analysis results, the A beta 42/A beta 40 ratio (AUC = 0.950, p < 0.01; 95%) performed significantly better than A beta 42 alone (AUC = 0.913, p < 0.01; 95%) in discriminating between AD patients and healthy controls and presented better diagnostic ability for AD. The novelties of this study are not only related to evaluating A beta peptides as AD biomarkers, but also to demonstrating direct online coupling of fiber-in-tube SPME with MS/MS as a quantitative high-throughput method for bioanalysis. (AU)

• Processo FAPESP: 19/19485-0 - Desenvolvimento de fibras de nitinol revestidas com líquidos iônicos poliméricos zwiteriônicos para a determinação de beta-amilóides em amostras de plasma de pacientes com doença de Alzheimer através do acoplamento direto fiber-in-tube SPME e MS/MS
• Beneficiário: Israel Donizeti de Souza
• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado
• Processo FAPESP: 20/00126-8 - Desenvolvimento de métodos de microextração hifenados à LC-MS/MS ou diretamente à MS/MS para a determinação de biomarcadores em amostras biológicas de pacientes ou de ratos com doenças neurodegenerativas
• Beneficiário: Maria Eugênia Queiroz Nassur
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 17/02147-0 - Cromatografia líquida em uma gota e seu acoplamento com espectrometria de massas: estratégias instrumentais, desenvolvimento de materiais, automatização e aplicações analíticas
• Beneficiário: Fernando Mauro Lanças
• Modalidade de apoio: Auxílio à Pesquisa - Temático